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. 2009 Mar;50(3):1093-7.
doi: 10.1167/iovs.08-1839. Epub 2008 May 23.

Genome-wide linkage scan in fuchs endothelial corneal dystrophy

Natalie A Afshari  1 , Yi-Ju Li, Margaret A Pericak-Vance, Simon Gregory, Gordon K Klintworth
Affiliations

Genome-wide linkage scan in fuchs endothelial corneal dystrophy

Natalie A Afshari et al. Invest Ophthalmol Vis Sci. 2009 Mar.

Abstract

Purpose: To perform a genome-wide linkage screen with a single-nucleotide polymorphism (SNP) linkage panel to identify regions of genetic linkage in Fuchs endothelial corneal dystrophy (FECD) and to analyze affected individuals for mutations in the COL8A2 gene.

Methods: Ninety-two individuals from 22 families with FECD were identified from our multiplex FECD family cohort. A genome-wide linkage scan was performed using an SNP linkage panel. Parametric two-point linkage analyses were calculated and nonparametric multipoint linkage analyses were performed on chromosomes with two-point LOD scores (HLOD) > 1.0. All affected individuals were analyzed for the two previously reported FECD mutations in the COL8A2 gene (L450W and Q455K).

Results: The genome-wide analysis identified five regions with linkage signals from all analyses on chromosomes 1, 7, 15, 17, and X. The highest two-point HLODs were found on the long arm of chromosome 15 with an HLOD of 3.26 for the recessive model and 2.48 for the dominant model. Multipoint linkage analysis also identified a linkage peak on the long arm of chromosome 15 with a LOD > 1. The region of linkage on chromosome 1p, driven by two multigenerational FECD families with a two-point LOD > 2, was adjacent to the previously identified COL8A2 gene; however, the two reported mutations in COL8A2 were not identified in any of the 56 affected individuals in the 92 samples tested.

Conclusions: Genome-wide linkage analysis was used to identify potential linkage regions on chromosomes 1, 7, 15, 17, and X for FECD. The previously reported mutations in the COL8A2 gene were not found in the 92 samples tested.

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Figures

FIGURE 1
FIGURE 1
Pedigree of the large multigenerational family in this study (family 1). +, individuals from whom DNA was obtained; filled symbols: affected individuals; numbers in diamond symbols: unaffected individuals; arrowhead: the proband.
FIGURE 2
FIGURE 2
Two-point and multipoint linkage results of chromosome 15 from all families. 2pt DOM, two-point linkage analysis dominant model; 2pt REC, two-point linkage analysis recessive model; Mpt LOD, multipoint linkage analysis LOD score.
See this image and copyright information in PMC

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